title: Physiological slowing and upregulation of inhibition in cortex are correlated with behavioral deficits in protein malnourished rats.
abstract: Protein malnutrition during early development has been correlated with cognitive and learning disabilities in children, but the neuronal deficits caused by long-term protein deficiency are not well understood. We exposed rats from gestation up to adulthood to a protein-deficient (PD) diet, to emulate chronic protein malnutrition in humans. The offspring exhibited significantly impaired performance on the 'Gap-crossing' (GC) task after reaching maturity, a behavior that has been shown to depend on normal functioning of the somatosensory cortex. The physiological state of the somatosensory cortex was examined to determine neuronal correlates of the deficits in behavior. Extracellular multi-unit recording from layer 4 (L4) neurons that receive direct thalamocortical inputs and layers 2/3 (L2/3) neurons that are dominated by intracortical connections in the whisker-barrel cortex of PD rats exhibited significantly low spontaneous activity and depressed responses to whisker stimulation. L4 neurons were more severely affected than L2/3 neurons. The response onset was significantly delayed in L4 cells. The peak response latency of L4 and L2/3 neurons was delayed significantly. In L2/3 and L4 of the barrel cortex there was a substantial increase in GAD65 (112% over controls) and much smaller increase in NMDAR1 (12-20%), suggesting enhanced inhibition in the PD cortex. These results show that chronic protein deficiency negatively affects both thalamo-cortical and cortico-cortical transmission during somatosensory information processing. The findings support the interpretation that sustained protein deficiency interferes with features of cortical sensory processing that are likely to underlie the cognitive impairments reported in humans who have suffered from prolonged protein deficiency.
authors.affiliation: National Brain Research Centre, Manesar, Haryana, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Chaudhary
authors.forename: Manisha
authors.initials: M
authors.lastname: Chugh
authors.forename: Ziauddin
authors.initials: Z
authors.lastname: Darokhan
authors.forename: Raghu Ram
authors.initials: RR
authors.lastname: Katreddi
authors.forename: Renuka
authors.initials: R
authors.lastname: Ramachandra
authors.forename: V
authors.initials: V
authors.lastname: Rema
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003071:Cognition / Q000502:physiology; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008297:Male; D044342:Malnutrition / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011488:Protein Deficiency / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time; D013003:Somatosensory Cortex / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission; D013788:Thalamus / Q000378:metabolism / Q000503:physiopathology*